Proteomics in IDH-mutated diffuse lower-grade glioma: a scoping review Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1093/noajnl/vdaf258
· OA: W4417308520
Background Therapeutic options and biomarkers for isocitrate dehydrogenase-mutated (IDHmut) diffuse lower-grade glioma (dLGG), WHO grade 2–3, are limited. Global quantitative proteomics has aided the discovery of novel markers and drug targets across various pathologies. This review aimed to summarize current proteomic findings in IDHmut dLGG. Methods PubMed, Embase, and Scopus were searched following PRISMA-ScR guidelines. Studies examining quantitative proteomics in IDHmut dLGG with liquid chromatography–mass spectrometry in adult human samples were included. Studies with only high-grade gliomas, without IDHmut, using xenografts, or cell line samples, and reviews were excluded. Results In total, 1,902 records were identified; 85 full-texts were retrieved, and 13 met the inclusion criteria. Twelve studies were cross-sectional and one longitudinal. Two studies used cerebrospinal fluid samples, while seven used fresh frozen and five formalin-fixed paraffin-embedded (FFPE) tissue samples. There was a large heterogeneity in aims, sample types, and analytical techniques. The most recurrent finding was altered energy metabolism, mostly related to the tricarboxylic acid cycle, compared to IDH-wildtype gliomas. IDHmut dLGG proteomic profile was distinct from other brain tumors, including IDH-wildtype glioblastoma, IDHmut grade 4 astrocytomas, and grade 1 gliomas or normal brain. Conclusions IDHmut dLGG has a unique proteome that may be leveraged for biomarkers and therapeutic discovery. Proteomic findings indicate a particular dependency on glutamate metabolism to sustain the citric acid cycle and energy production. Although current proteomic knowledge is limited and fragmented, technological advancements present an opportunity for large-scale studies using FFPE samples, advancing proteomic knowledge and precision medicine in IDHmut dLGG.
